A TISSUE-SPECIFIC TRANSCRIPTION FACTOR CONTAINING A HOMEODOMAIN SPECIFIES A PITUITARY PHENOTYPE
A TISSUE-SPECIFIC TRANSCRIPTION FACTOR CONTAINING A HOMEODOMAIN SPECIFIES A PITUITARY PHENOTYPE
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DOI：
10.1016/0092-8674(88)90038-4
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发表时间：
1988-11-04
期刊：
影响因子：
64.5
通讯作者：
ROSENFELD, MG
中科院分区：
文献类型：
--
作者：
INGRAHAM, HA;CHEN, R;ROSENFELD, MG
大鼠催乳素基因的细胞特异性激活所需的多个相关顺式活性元件似乎与垂体特异性正转录因子（称为Pit-1）结合。与Pit-1 mRNA互补的DNA，在特异性结合到大鼠催乳素和生长激素基因中富含AT的细胞特异性元件的基础上克隆，编码33 kd蛋白，其羧基末端与果蝇发育基因编码的同源结构域具有显著的相似性。Pit-1 mRNA仅在垂体前叶的促生长素细胞和促乳素细胞中表达，这两种细胞分别产生生长激素和催乳素。Pit-1在异源细胞（HeLa）中的表达选择性地激活催乳素和生长激素融合基因表达，表明Pit-1足以赋予特征性垂体表型。Pit-1及其识别元件的结构表明，后生动物的组织表型是由一个家族的转录因子，结合相关的顺式活性元件，并含有几个高度保守的结构域。
Multiple related cis-active elements required for cell-specific activation of the rat prolactin gene appear to bind a pituitary-specific positive transcription factor(s), referred to as Pit-1. DNA complementary to Pit-1 mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes. Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively. Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype. The structure of Pit-1 and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related cis-active elements and contain several highly conserved domains.